[NMR paper] Structural characterisation of high affinity Siglec-2 (CD22) ligands in complex with whole Burkitt's lymphoma (BL) Daudi cells by NMR spectroscopy.
Related ArticlesStructural characterisation of high affinity Siglec-2 (CD22) ligands in complex with whole Burkitt's lymphoma (BL) Daudi cells by NMR spectroscopy.
Sci Rep. 2016 11 03;6:36012
Authors: Madge PD, Maggioni A, Pascolutti M, Amin M, Waespy M, Bellette B, Thomson RJ, Kelm S, von Itzstein M, Haselhorst T
Abstract
Siglec-2 undergoes constitutive endocytosis and is a drug target for autoimmune diseases and B cell-derived malignancies, including hairy cell leukaemia, marginal zone lymphoma, chronic lymphocytic leukaemia and non-Hodgkin's lymphoma (NHL). An alternative to current antibody-based therapies is the use of liposomal nanoparticles loaded with cytotoxic drugs and decorated with Siglec-2 ligands. We have recently designed the first Siglec-2 ligands (9-biphenylcarboxamido-4-meta-nitrophenyl-carboxamido-Neu5Ac?2Me, 9-BPC-4-mNPC-Neu5Ac?2Me) with simultaneous modifications at C-4 and C-9 position. In the current study we have used Saturation Transfer Difference (STD) NMR spectroscopy to monitor the binding of 9-BPC-4-mNPC-Neu5Ac?2Me to Siglec-2 present on intact Burkitt's lymphoma Daudi cells. Pre-treatment of cells with periodate resulted in significantly higher STD NMR signal intensities for 9-BPC-4-mNPC-Neu5Ac?2Me as the cells were more susceptible to ligand binding because cis-binding on the cell surface was removed. Quantification of STD NMR effects led to a cell-derived binding epitope of 9-BPC-4-mNPC-Neu5Ac?2Me that facilitated the design and synthesis of C-2, C-3, C-4 and C-9 tetra-substituted Siglec-2 ligands showing an 88-fold higher affinity compared to 9-BPC-Neu5Ac?2Me. This is the first time a NMR-based binding study of high affinity Siglec-2 (CD22) ligands in complex with whole Burkitt's lymphoma Daudi cells has been described that might open new avenues in developing tailored therapeutics and personalised medicine.
Affinity screening using competitive binding with fluorine-19 hyperpolarized ligands
From The DNP-NMR Blog:
Affinity screening using competitive binding with fluorine-19 hyperpolarized ligands
Kim, Y. and C. Hilty, Affinity screening using competitive binding with fluorine-19 hyperpolarized ligands. Angew Chem Int Ed Engl, 2015. 54(16): p. 4941-4.
http://www.ncbi.nlm.nih.gov/pubmed/25703090
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10-08-2015 12:56 AM
[NMR paper] SEAL by NMR: Glyco-Based Selenium-Labeled Affinity Ligands Detected by NMR Spectroscopy.
SEAL by NMR: Glyco-Based Selenium-Labeled Affinity Ligands Detected by NMR Spectroscopy.
Related Articles SEAL by NMR: Glyco-Based Selenium-Labeled Affinity Ligands Detected by NMR Spectroscopy.
Chemistry. 2014 Sep 5;
Authors: Hamark C, Landström J, Widmalm G
Abstract
We report a method for the screening of interactions between proteins and selenium-labeled carbohydrate ligands. SEAL by NMR is demonstrated with selenoglycosides binding to lectins where the selenium nucleus serves as an NMR-active handle and reports on binding...
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09-10-2014 11:24 AM
[NMR paper] Ranking high affinity ligands of low solubility by NMR spectroscopy.
Ranking high affinity ligands of low solubility by NMR spectroscopy.
Related Articles Ranking high affinity ligands of low solubility by NMR spectroscopy.
ACS Med Chem Lett. 2011 Jun 9;2(6):485-7
Authors: Landrieu I, Hanoulle X, Fritzinger B, Horvath D, Wieruszeski JM, Lippens G
Abstract
Cyclosporine A (CsA) and its chemical analogues EthVal4Cs, MeVal4Cs, and Me(d-Ala)3EthVal4Cs (Alisporivir) all interact with cyclophilin A (CypA). The latter Alisporivir is a nonimmunosuppressive CsA derivative that has potent anti-HCV properties...
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06-07-2014 07:12 PM
[NMR paper] NMR screening of new carbocyanine dyes as ligands for affinity chromatography.
NMR screening of new carbocyanine dyes as ligands for affinity chromatography.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--media.wiley.com-assets-2250-98-WileyOnlineLibrary-Button_120x27px_FullText.gif Related Articles NMR screening of new carbocyanine dyes as ligands for affinity chromatography.
J Mol Recognit. 2014 Apr;27(4):197-204
Authors: Cruz C, Boto RE, Drzazga AK, Almeida P, Queiroz JA
Abstract
Four new carbocyanines containing symmetric and asymmetric heterocyclic moieties and N-carboxyalkyl groups have...
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03-05-2014 11:57 PM
[NMR paper] Red wines attenuate TNF? production in human histiocytic lymphoma cell line: an NMR spectroscopy and chemometrics based study.
Red wines attenuate TNF? production in human histiocytic lymphoma cell line: an NMR spectroscopy and chemometrics based study.
Related Articles Red wines attenuate TNF? production in human histiocytic lymphoma cell line: an NMR spectroscopy and chemometrics based study.
Food Chem. 2013 Dec 1;141(3):3124-30
Authors: Ali K, Iqbal M, Fortes AM, Pais MS, Korthout HA, Verpoorte R, Choi YH
Abstract
Nuclear magnetic resonance (NMR) spectroscopy and multivariate data analyses methods are applied to the metabolic profiling of different red wines...
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02-02-2014 12:08 AM
[NMR paper] Competition STD NMR for the detection of high-affinity ligands and NMR-based screenin
Competition STD NMR for the detection of high-affinity ligands and NMR-based screening.
Related Articles Competition STD NMR for the detection of high-affinity ligands and NMR-based screening.
Magn Reson Chem. 2004 Jun;42(6):485-9
Authors: Wang YS, Liu D, Wyss DF
The reported competition STD NMR method combines saturation transfer difference (STD) NMR with competition binding experiments to allow the detection of high-affinity ligands that undergo slow chemical exchange on the NMR time-scale. With this technique, the presence of a competing...
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11-24-2010 09:51 PM
[NMR paper] NMR probing of protein-protein interactions using reporter ligands and affinity tags.
NMR probing of protein-protein interactions using reporter ligands and affinity tags.
Related Articles NMR probing of protein-protein interactions using reporter ligands and affinity tags.
J Am Chem Soc. 2004 Feb 18;126(6):1636-7
Authors: Ludwiczek ML, Baminger B, Konrat R
A novel method is proposed for the detection and quantification of protein-protein interactions in solution. In this approach, one protein binding partner is tagged with a ligand binding domain, and protein-protein interaction is monitored via changes in the NMR relaxation...
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11-24-2010 09:25 PM
[NMR paper] Discovering high-affinity ligands for proteins: SAR by NMR.
Discovering high-affinity ligands for proteins: SAR by NMR.
Related Articles Discovering high-affinity ligands for proteins: SAR by NMR.
Science. 1996 Nov 29;274(5292):1531-4
Authors: Shuker SB, Hajduk PJ, Meadows RP, Fesik SW
A nuclear magnetic resonance (NMR)-based method is described in which small organic molecules that bind to proximal subsites of a protein are identified, optimized, and linked together to produce high-affinity ligands. The approach is called "SAR by NMR" because structure-activity relationships (SAR) are obtained from...
Structural characterisation of high affinity Siglec-2 (CD22) ligands in complex with whole Burkitt's lymphoma (BL) Daudi cells by NMR spectroscopy.
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